Soft bioelectronic technologies for selective and multimodal peripheral nerve interfaces

The peripheral nervous system (PNS) regulates the exchange of sensory information andmotor commands between the body and the central nervous system. Further, through theautonomic nervous system, the PNS plays a pivotal role in controlling vital physiologicalprocesses. For treating various PNS-related and non-neurological conditions, neurotechnologiesinterfacing with the PNS are critical. Yet, precisely stimulating or inhibiting targetfibers remains a significant challenge due to the complex morphology and composition ofnerves. Traditional peripheral nerve interfaces, relying on electrical stimulation, grapple witha problematic tradeoff between selectivity and invasiveness. Extraneural cuff electrodes areconsidered the safest yet least selective. Cuffs present other issues too, like lead migration,fracture, infection, and nerve injury, often due to inadequate sizing and use of rigid/compressivematerials.This thesis introduces an approach to tackle these obstacles through the development of a softperipheral nerve interface. The system's translational potential was experimentally validatedin small and large animal models. Moreover, the interface was designed to incorporate opticalstimulation functionality, allowing for advanced selective stimulation strategies.The first part of the work centers on the development of a soft, adaptable cuff electrode. Usinga 150 µm silicone layer (E~1 MPa) as the base material, and incorporating stretchable thin-filmgold tracks, the cuff was designed to adapt to a range of nerve sizes and shapes. It features aunique belt-like structure, ensuring near-complete perimeter coverage and facilitating implantation.Electrochemical characterization and rat sciatic nerve testing confirmed the device'sstable performance across varying conditions. The cuff's applicability was further demonstratedin translational applications involving pig sciatic nerve stimulation and vagus nerverecording. The 16-channel stimulating cuff demonstrated the ability to selectively activate upto five muscles, with comparable and improved performances to existing systems.Additionally, integration of rigid light sources within a soft cuff for opto-modulation wasexplored. Despite initial challenges related to strain gradients in soft-rigid systems, the developedcuff maintained conformability and LED functionality while stretching (~ 35% strain).As a proof-of-concept, spatially distinct stimulation of sciatic nerve from four separate sites was demonstrated, indicating potential for high-density, stretchable optoelectronic interfaces.Lastly, nerve-on-a-chip systems were leveraged ex vivo to explore novel peripheral neuromodulationstrategies. These platforms, which amplify and track propagating action potentialsfrom explanted nerve rootlets, hold great promise for elucidating the complex mechanismsbehind ultrasonic and optical stimulation techniques, and for optimizing strategies before invivo validation.In conclusion, this work contributes to simplifying the implantation procedure of cuffs, enablingintimate contact with varying nerve sizes, achieving remarkable selectivity even incomplex fascicular organization and providing an improved chronic (6-week) biointegration.Furthermore, the integration of optical stimulation and the development of ex vivo testingstrategies propels the optimization and characterization of novel modulation methods, thusenhancing our understanding of peripheral neural mechanisms.